Short-term exposures to high levels of ozone appear to increase the risk of perforated appendicitis, researchers reported.

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Short-term exposures to high levels of ozone appear to increase the risk of perforated appendicitis.

Note that it remains unclear whether the link is causal or whether ozone levels could be a marker for other factors that cause the appendicitis increase.

Short-term exposures to high levels of ozone appear to increase the risk of perforated appendicitis, researchers reported.

In a 5-year case-crossover study in 12 Canadian cities, a week of increased ozone levels was associated with a 7% increase in the risk of appendicitis, according to Gilaad Kaplan, MD, of the University of Calgary in Calgary, Alberta, and colleagues.

But the increase was almost entirely driven by a 22% rise in cases of perforated appendicitis, Kaplan and colleagues reported online in Environmental Health Perspectives.

The finding supports the notion that perforated appendicitis is "a distinct phenotype with diverging pathogenesis from nonperforated appendicitis," Kaplan and colleagues argued.

They noted that appendicitis is relatively common and has a significant impact on the healthcare system and on patients, but its pathogenesis is largely unknown.

However, they added, there is some evidence that the disease has an environmental component, including a decrease in incidence that followed legislation that controlled several pollutants in the late 20th century.

To examine the idea further, they used hospital discharge data to examine rates of appendicitis in 12 Canadian cities from Jan. 1, 2004 through Dec. 31, 2008.

Because of an earlier pilot study in Calgary that found a positive association between ambient ozone and appendicitis, they compared disease rates with daily maximum ozone concentrations.

Over the study period, they determined that 35,811 people were admitted to hospitals with appendicitis, based on both a diagnostic ICD-10 code for the disease and a procedural code for appendectomy.

The case-crossover design used participants as their own controls, Kaplan and colleagues noted. For each case, air pollution exposure on the day of appendicitis admission (the "index day") was compared with exposure on several referent days -- the same weekday during the same month and year as the index day.

The patients had a median age of 30, 55% were male, and 31% had perforated appendicitis. In the 12 cities, the median daily maximum ozone concentration was 33.3 parts per billion, with an interquartile range of 16 parts per billion.

For perforated appendicitis, the risk increased as the time period of exposure rose -- the 3-day odds ratio was 1.11, compared with 1.15 for 5 days, and 1.22 for the 7-day average daily maximum concentration. All the odds ratios reached significance.

Ozone exposure was not associated with nonperforated appendicitis regardless of length of exposure. For instance, the 7-day odds ratio was 1.02, but the 95% confidence interval ranged from 0.95 to 1.09.

The odds ratios did not vary significantly by age, sex, or season, Kaplan and colleagues reported.

The investigators cautioned that it remains unclear whether the link between elevated ozone and increased risk of perforated appendicitis is causal. Among other possibilities, it could be a marker for other factors that do cause the increase.

They also noted that the ozone measurements were regional and not related to individual patients. They were also ambient and may not have reflected indoor exposure.

Statistically, Kaplan and colleagues cautioned, multiple comparisons might have led to some findings that appeared significant purely by chance.

The study was supported by the Canadian Institutes of Health Research and Health Canada.

The journal said none of the authors had relevant disclosures to declare.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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